Less remineralized carbon in the intermediate-depth south Atlantic during Heinrich Stadial 1

Author Posting. © American Geophysical Union, 2019. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography and Paleoclimatology, 34(7), (2019): 1218-1233, doi:10.1029/2018PA003537.The last deglaciation (~20–10 kyr BP) was characterized by a major shift in Earth's climate state, when the global mean surface temperature rose ~4 °C and the concentration of atmospheric CO2 increased ~80 ppmv. Model simulations suggest that the initial 30 ppmv rise in atmospheric CO2 may have been driven by reduced efficiency of the biological pump or enhanced upwelling of carbon‐rich waters from the abyssal ocean. Here we evaluate these hypotheses using benthic foraminiferal B/Ca (a proxy for deep water [CO32−]) from a core collected at 1,100‐m water depth in the Southwest Atlantic. Our results imply that [CO32−] increased by 22 ± 2 μmol/kg early in Heinrich Stadial 1, or a decrease in ΣCO2 of approximately 40 μmol/kg, assuming there were no significant changes in alkalinity. Our data imply that remineralized phosphate declined by approximately 0.3 μmol/kg during Heinrich Stadial 1, equivalent to 40% of the modern remineralized signal at this location. Because tracer inversion results indicate remineralized phosphate at the core site reflects the integrated effect of export production in the sub‐Antarctic, our results imply that biological productivity in the Atlantic sector of the Southern Ocean was reduced early in the deglaciation, contributing to the initial rise in atmospheric CO2.We would like to thank Bärbel Hönisch at Lamont‐Doherty Earth Observatory of Columbia University for help with methods development and Sarah McCart for technical assistance with ICP‐MS analyses. We would also like to give special thanks to Anna lisa Mudahy, who was responsible for picking a substantial portion of the benthic foraminifera used in this study. We are grateful to the WHOI core lab for sample collection and archiving. This work was supported by NSF grant OCE‐1702231 to D. L.2020-01-2

The potential of antisense oligonucleotide therapies for inherited childhood lung diseases.

Antisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient's genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading frame, target an RNA transcript for degradation through RNaseH activation, block ribosome initiation of protein translation or disrupt miRNA function. The recent accelerated approval of eteplirsen (renamed Exondys 51™) by the Food and Drug Administration, for the treatment of Duchenne muscular dystrophy, and nusinersen, for the treatment of spinal muscular atrophy, herald a new and exciting era in splice-switching antisense oligonucleotide applications to treat inherited diseases. This review considers the potential of antisense oligonucleotides to treat inherited lung diseases of childhood with a focus on cystic fibrosis and disorders of surfactant protein metabolism

Faithful chaperones

This review describes the properties of some rare eukaryotic chaperones that each assist in the folding of only one target protein. In particular, we describe (1) the tubulin cofactors, (2) p47, which assists in the folding of collagen, (3) α-hemoglobin stabilizing protein (AHSP), (4) the adenovirus L4-100 K protein, which is a chaperone of the major structural viral protein, hexon, and (5) HYPK, the huntingtin-interacting protein. These various-sized proteins (102–1,190 amino acids long) are all involved in the folding of oligomeric polypeptides but are otherwise functionally unique, as they each assist only one particular client. This raises a question regarding the biosynthetic cost of the high-level production of such chaperones. As the clients of faithful chaperones are all abundant proteins that are essential cellular or viral components, it is conceivable that this necessary metabolic expenditure withstood evolutionary pressure to minimize biosynthetic costs. Nevertheless, the complexity of the folding pathways in which these chaperones are involved results in error-prone processes. Several human disorders associated with these chaperones are discussed

Hb Foggia or alpha 117(GH5)Phe -> Ser: a new alpha 2 globin allele affecting the alpha Hb-AHSP interaction

We report a novel α2-globin gene allele with the mutation cod 117 TTC>TCC or α117(GH5)Phe>Ser detected in three carriers with α-thalassemia phenotype. The mutated mRNA was present in the reticulocytes in the same amount as the normal one, but no chain or hemoglobin variant were detected. Most likely the amino acid substitution impairs the interaction of the α-chain variant with the AHSP and prevents its stabilizing effect, thus leading to the α-chain pool reductio

HB City of Hope [β69(E13)GLSER] in Italy: Association of the Gene with Haplotype IX

Hb City of Hope [β69(E13)GLSER] was detected by reversed phase high performance liquid chromatography in an asymptomatic carrier from Naples, Southern Italy. The amino acid substitution, identified by fast atom bombardment mass spectrometry, was due to a TGGA substitution as assessed by DNA sequencing. Analysis of the chromosomal background indicates that the globin gene cluster containing the mutant gene has most probably been rearranged by a recombination event, since the mutation was associated with restriction fragment length polymorphism haplotype IX, instead of haplotype I, as previously reported